Quality and methods of developing practice guidelines

BACKGROUND: It is not known whether there are differences in the quality and recommendations between evidence-based (EB) and consensus-based (CB) guidelines. We used breast cancer guidelines as a case study to assess for these differences. METHODS: Five different instruments to evaluate the quality of guidelines were identified by a literature search. We also searched MEDLINE and the Internet to locate 8 breast cancer guidelines. These guidelines were classified in three categories: evidence based, consensus based and consensus based with no explicit consideration of evidence (CB-EB). Each guideline was evaluated by three of the authors using each of the instruments. For each guideline we assessed the agreement among 14 decision points which were selected from the NCCN (National Cancer Comprehensive Network) guidelines algorithm. For each decision point we recorded the level of the quality of the information used to support it. A regression analysis was performed to assess if the percentage of high quality evidence used in the guidelines development was related to the overall quality of the guidelines. RESULTS: Three guidelines were classified as EB, three as CB-EB and two as CB. The EB guidelines scored better than CB, with the CB-EB scoring in the middle among all instruments for guidelines quality assessment. No major disagreement in recommendations was detected among the guidelines regardless of the method used for development, but the EB guidelines had a better agreement with the benchmark guideline for any decision point. When the source of evidence used to support decision were of high quality, we found a higher level of full agreement among the guidelines' recommendations. Up to 94% of variation in the quality score among guidelines could be explained by the quality of evidence used for guidelines development. CONCLUSION: EB guidelines have a better quality than CB guidelines and CB-EB guidelines. Explicit use of high quality evidence can lead to a better agreement among recommendations. However, no major disagreement among guidelines was noted regardless of the method for their development

Donnan effect on chloride ion distribution as a determinant of body fluid composition that allows action potentials to spread via fast sodium channels

Proteins in any solution with a pH value that differs from their isoelectric point exert both an electric Donnan effect (DE) and colloid osmotic pressure. While the former alters the distribution of ions, the latter forces water diffusion. In cells with highly Cl--permeable membranes, the resting potential is more dependent on the cytoplasmic pH value, which alters the Donnan effect of cell proteins, than on the current action of Na/K pumps. Any weak (positive or negative) electric disturbances of their resting potential are quickly corrected by chloride shifts

Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections

G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer

BACKGROUND: G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis. RESULTS: In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I). CONCLUSIONS: These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs

Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

<p>Abstract</p> <p>Background</p> <p>Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As₂O₃) with cisplatin (DDP) on A549 and H460 non-small cell lung cancer (NSCLC) cells were explored.</p> <p>Methods</p> <p>A549 and H460 human lung cancer cells were treated with As₂O₃and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, clonogenic assay, and flow cytometry (FCM). Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot.</p> <p>Results</p> <p>MTT and clonogenic assay showed As₂O₃within 10^-2μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As₂O₃exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI) for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As₂O₃with DDP. FCM showed As₂O₃did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As₂O₃and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As₂O₃and/or DDP. FCM and TUNEL staining illustrated that the combination of As₂O₃and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As₂O₃and/or DDP treatments compared with controls. The expression of caspase-3 in cells treated with the combination of As₂O₃and DDP did not differ from that in cells treated with a single agent.</p> <p>Conclusion</p> <p>As₂O₃exerted synergistic effects with DDP on NSCLC cells, and the synergistic effects were partly due to the induction of caspase-independent apoptosis.</p

Invasive carcinomas of the male breast: a morphologic study of the distribution of histologic subtypes and metastatic patterns in 778 cases

The current investigation was conducted to evaluate the proportional distribution of the various histologic subtypes (including newly recognized variants) of male breast carcinomas, to determine whether any histologic subtypes occur with a frequency that is markedly discordant with the expected frequencies from published data on parallel female breast tumors. We also aimed to document the distribution of malignancies metastatic to the breast. Seven hundred fifty-nine archived cases of primary invasive carcinoma involving the male breast were retrieved and subcategorized into histologic subtypes according to contemporary criteria. Six hundred forty-three (84.7%) tumors were pure infiltrating ductal carcinoma (IDC) not otherwise specified. The most common of the remainder included papillary carcinoma with invasion in the form of IDC (n = 34), mixed IDC and mucinous carcinoma (n = 26), and pure mucinous carcinoma (n = 21). In 19 cases, metastases from other sites involved the breast, most commonly (58%) cutaneous melanoma. Invasive carcinoma of the male breast appears to display a morphologic spectrum and distribution of histologic subtypes that is comparable to those of the female breast, with some expected variation. Compared with published experience on their female counterparts, there is a two-fold increase in the frequency of invasive papillary carcinoma in the male breast. Finally, the most common tumor metastatic to the male breast in this series was cutaneous melanoma

A Systematic Evaluation of the Impact of STRICTA and CONSORT Recommendations on Quality of Reporting for Acupuncture Trials

Background: We investigated whether there had been an improvement in quality of reporting for randomised controlled trials of acupuncture since the publication of the STRICTA and CONSORT statements. We conducted a before-and-after study, comparing ratings for quality of reporting following the publication of both STRICTA and CONSORT recommendations. Methodology and Principal Findings: Ninety peer reviewed journal articles reporting the results of acupuncture trials were selected at random from a wider sample frame of 266 papers. Papers published in three distinct time periods (1994–1995, 1999–2000 and 2004–2005) were compared. Assessment criteria were developed directly from CONSORT and STRICTA checklists. Papers were independently assessed for quality of reporting by two assessors, one of whom was blind to information which could have introduced systematic bias (e.g. date of publication). We detected a statistically significant increase in the reporting of CONSORT items for papers published in each time period measured. We did not, however, find a difference between the number of STRICTA items reported in journal articles published before and 3 to 4 years following the introduction of STRICTA recommendations. Conclusions and Significance: The results of this study suggest that general standards of reporting for acupuncture trials have significantly improved since the introduction of the CONSORT statement in 1996, but that quality in reporting detail

Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck

CD9 is a transmembrane protein that has been implicated in cell adhesion, motility and proliferation, and numerous studies have demonstrated the prognostic value of its expression in different solid tumours. The purpose of this study is to determine the predictive value of CD9 in squamous cell carcinoma (SCC) of the head and neck. A total of 153 cases were examined for CD9 expression using immunohistochemistry applied on formalin-fixed, paraffin-embedded tissue. Cases were stratified in two categories depending on CD9 expression, as positive (>/=50% positive cells) or reduced (<50%). In all, 108 cases were positive for CD9 (85 cases with membranous, and 23 with both membranous and cytoplasmic staining) and 45 reduced expression. Reduced CD9 expression was significantly associated with high grade (P=0.0007) and lower disease-free survival (DFS) (P=0.017). The latter retained its significance in the multivariate analysis. When the 23 cases with both membranous and cytoplasmic patterns were studied as a separate subgroup, there were significant associations between CD9 expression and tumour grade (P=0.025) (95% CI 11-68), tumour stage (P=0.08) (95% CI 3.5-86) and the occurrence of any failure (P=0.083) (95% CI -1.7-57). Immunohistochemical CD9 expression proved to be an independent prognostic factor in SCC of the head and neck, and it may detect patients at a high risk of recurrence. In addition, the cytoplasmic pattern seems to have an even more significant value. However, this finding is limited to the small number of cases with this pattern